The purpose of this project is to understand the regulation of TGF-Betas by members of the steroid hormone superfamily. Studies with mouse keratinocytes have demonstrated that retinoids increased TGF-82 mRNA and protein at a post-transcriptional level, while having little effect on TGF-Beta1 expression. Anti-estrogens increased translation of TGF-Beta1 in human fibroblasts, and the progestin analog, gestodene, increased TGF-Beta1 expression at both transcriptional and post-transcriptional levels in a breast carcinoma cell line. In mouse keratinocytes and the breast carcinoma cell line, increased levels of TGF-Beta were correlated with suppression of cell growth. Furthermore, the growth inhibitory effects of retinoids and gestodene were reversed by neutralizing antibodies against TGF-Beta. These studies have demonstrated that the action of steroids on the expression of TGF-Beta are distinct and specific for the various types of TGF-Beta. Moreover, the increase in expression of TGF-Betas in response to members of the steroid hormone superfamily suggest that steroids may be useful as chemoprevention agents.